The HLA Research Group, Brain Sciences Center (11B), Department of Veterans Affairs Health Care System, Minneapolis VAHCS, One Veterans Drive, Minneapolis, MN, 55417, USA.
Department of Neuroscience, University of Minnesota Medical School, Minneapolis, MN, 55455, USA.
Sci Rep. 2023 May 26;13(1):8545. doi: 10.1038/s41598-023-35305-2.
Substance use disorders (SUDs) are common and costly conditions that are partially attributable to genetic factors. In light of immune system influences on neural and behavioral aspects of addiction, the present study evaluated the influence of genes involved in the human immune response, human leukocyte antigen (HLA), on SUDs. We used an immunogenetic epidemiological approach to evaluate associations between the population frequencies of 127 HLA alleles and the population prevalences of six SUDs (alcohol, amphetamine, cannabis, cocaine, opioid, and "other" dependence) in 14 countries of Continental Western Europe to identify immunogenetic profiles of each SUD and evaluate their associations. The findings revealed two primary groupings of SUDs based on their immunogenetic profiles: one group comprised cannabis and cocaine, whereas the other group comprised alcohol, amphetamines, opioids, and "other" dependence. Since each individual possesses 12 HLA alleles, the population HLA-SUD scores were subsequently used to estimate individual risk for each SUD. Overall, the findings highlight similarities and differences in immunogenetic profiles of SUDs that may influence the prevalence and co-occurrence of problematic SUDs and may contribute to assessment of SUD risk of an individual on the basis of their HLA genetic makeup.
物质使用障碍（SUD）是常见且代价高昂的疾病，部分归因于遗传因素。鉴于免疫系统对成瘾的神经和行为方面的影响，本研究评估了参与人类免疫反应的基因，即人类白细胞抗原（HLA），对 SUD 的影响。我们采用免疫遗传流行病学方法，评估了 127 种 HLA 等位基因在人群中的频率与六种 SUD（酒精、安非他命、大麻、可卡因、阿片类药物和“其他”依赖）在 14 个西欧大陆国家中的人群流行率之间的关联，以确定每种 SUD 的免疫遗传特征，并评估它们之间的关联。研究结果显示，基于免疫遗传特征，SUD 可分为两组：一组包括大麻和可卡因，另一组包括酒精、安非他命、阿片类药物和“其他”依赖。由于每个人都拥有 12 种 HLA 等位基因，因此随后使用人群 HLA-SUD 评分来估计每个人对每种 SUD 的风险。总体而言，研究结果突出了 SUD 的免疫遗传特征的相似性和差异性，这些特征可能会影响有问题的 SUD 的流行和共病发生，并有助于根据个体的 HLA 遗传构成来评估 SUD 风险。
